A great deal has been learned about the structure and function of human histocompatibility antigens in the past thirty years. Some details remain to be elucidated but, in addition, the information already obtained can be used to explore the relationship of these proteins to human diseases. The specific aims of this application are: 1. To develop murine models of pemphigus vulgaris employing human genes and to use these models to identify disease-related peptide epitopes bound to human Class 11 MHC proteins. 2. To examine the relationship between HLA-DP (a Class II MHC protein) and Hard Metal Diseases. 3. To examine the basis of the reactivity of a subset of HLA-B27 molecules (a class I MHC protein linked to ankylosing spondylitis) with an unusual monoclonal antibody MARB-4 and whether this subset might be related to the disease. 4. To examine the basis for the effectiveness of Copolymer 1 in the treatment of multiple sclerosis [genetically linked to the Class II MHC protein HLA-DR2 (DRB1*1501)] and to examine the possibility that more effective copolymers could be designed for the therapy of this disease, as well as for the therapy of the autoimmune disease (i.e. rheumatoid arthritis). 5. To utilize oligomerized T cell epitopes to study mouse models of, multiple sclerosis and pemphigus vulgaris, both of which are linked to specific alleles of Class II MHC genes.